CpG site-specific methylation as epi-biomarkers for the prediction of health risk in PAHs-exposed populations

• Published in: Journal of hazardous materials Vol. 431; p. 128538
• Main Authors: Ye, Lizhu, He, Zhini, Li, Daochuan, Chen, Liping, Chen, Shen, Guo, Ping, Yu, Dianke, Ma, Lu, Niu, Yong, Duan, Huawei, Xing, Xiumei, Xiao, Yongmei, Zeng, Xiaowen, Wang, Qing, Dong, Guanghui, Aschner, Michael, Zheng, Yuxin, Chen, Wen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.06.2022
• Subjects: Biomarkers - metabolism; blood; Coke - analysis; diesel engines; DNA Damage; DNA Methylation; dose response; Epi-biomarkers; health effects assessments; Humans; Occupational Exposure - analysis; ovens; Polycyclic aromatic hydrocarbons (PAHs) exposed subjects; Polycyclic Aromatic Hydrocarbons - analysis; Polycyclic Aromatic Hydrocarbons - toxicity; prediction; risk; Risk assessment; Specific genes; Polycyclic aromatic hydrocarbons (PAHs) exposed subjects; RASSF1a; DNA damage; OTM; C-index; BaP; DEs; Risk assessment; DNA methylation; CpG; HPLC; BMI; R2; COEs; MGMT; BMGV; PBLCs; Specific genes; r; BPA; 1-OHP; TEF; PAHs; TRIM36; epi-biomarkers; Epi-biomarkers
• ISSN: 0304-3894; 1873-3336; 1873-3336
• DOI: 10.1016/j.jhazmat.2022.128538

Environmental insults can lead to alteration in DNA methylation of specific genes. To address the role of altered DNA methylation in prediction of polycyclic aromatic hydrocarbons (PAHs) exposure-induced genetic damage, we recruited two populations, including diesel engine exhausts (low-level) and coke oven emissions (high-level) exposed subjects. The positive correlation was observed between the internal exposure marker (1-hydroxypyrene) and the extents of DNA damage (P < 0.05). The methylation of representative genes, including TRIM36, RASSF1a, and MGMT in peripheral blood lymphocytes was quantitatively examined by bisulfite-pyrosequencing assay. The DNA methylation of these three genes in response to PAHs exposure were changed in a CpG-site-specific manner. The identified hot CpG site-specific methylation of three genes exhibited higher predictive power for DNA damage than the respective single genes in both populations. Furthermore, the dose-response relationship analysis revealed a nonlinear U-shape curve of TRIM36 or RASSF1a methylation in combined population, which led to determination of the threshold of health risk. Furthermore, we established a prediction model for genetic damage based on the unidirectional-alteration MGMT methylation levels. In conclusion, this study provides new insight into the application of multiple epi-biomarkers for health risk assessment upon PAHs exposure. [Display omitted]